A Study of the Oral Farnesoid X Receptor Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B Patients in Combination With Pegylated Interferon alpha2a Alone and With Entecavir
- Conditions
- Hepatitis B, Chronic
- Interventions
- Registration Number
- NCT04365933
- Lead Sponsor
- Enyo Pharma
- Brief Summary
This is a multi centre, two parallel arm, randomized, open-label, Phase 2a experimental study of oral Farnesoid X Receptor (FXR) modulator EYP001a to assess its safety and anti-viral effect when administered to non-treated (treatment naive or off treatment) chronic Hepatitis B (CHB) patients in combination with entecavir (ETV) and pegylated interferon alpha2a (peg-IFN). An experimental treatment period of 16 weeks will be followed by a 24 week maintenance period with ETV standard of care (SoC).
- Detailed Description
In total 30 eligible patients will be enrolled and randomized at approximately 7 study sites.
Patients will be randomized prior to study drug (EYP001a, ETV and peg-IFN) administration on Day 1 in the ratio of 1:1 into 2 treatment arms:
* Arm 1: EYP001a QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
* Arm 2: EYP001a QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 37 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify for study drug administration on Day 1.
The visits during the study are planned as below:
* Screening visit: 5 weeks (37 days)
* 16 weeks treatment period
* 24 weeks maintenance period. During maintenance period patients are kept on ETV until the end of the trial at Week 40.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
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Has given voluntary written informed consent before performance of any study related procedure.
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Are treatment naive or without HBV treatment for at least 60 days or 5 times the elimination half-life, whichever is longer.
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Patient has CHB:
- HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
- HBsAg ≥ 2.5 log10 IU/mL.
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Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
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Patient is not of childbearing potential or, if of childbearing potential, is not pregnant as confirmed by a negative serum human chorionic gonadotropin test at screening and is not planning a pregnancy during the course of the study.
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Is an employee of a clinical research organization, vendor, or Sponsor involved with this study.
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Has known hepatocellular carcinoma or pancreaticobiliary disease.
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Neutropenia (defined by two confirmed values during Screening period of < 1500/μL).
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Has Gilbert syndrome.
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Shows evidence of worsening liver tests, defined as either a confirmed (2 assessments at least 3 days apart) increase > 2 ULN ALT or AST or an increase of > 1.5 × baseline value of TBL or associated with clinical signs or symptoms of liver impairment.
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Has known or suspected non-CHB liver disease
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History of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of oesophageal varices.
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Probable or possible F4 stage with a vibration controlled transient elastography (VCTE) > 11.7 kPa leads to exclusion
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Has known history of alcohol abuse or daily heavy alcohol consumption
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Has any of the following exclusionary laboratory results at screening:
- ALT > 2 × ULN, AST > 2 × ULN
- INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
- Platelet count < 100 G/L
- Estimated glomerular filtration rate < 50 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
- Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 EYP001a EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW Arm 1 Pegylated interferon alpha2a EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW Arm 2 EYP001a EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW Arm 2 Pegylated interferon alpha2a EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW Arm 1 Entecavir EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
- Primary Outcome Measures
Name Time Method Measurement of HBsAg decline 16 weeks Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period
Number of Treatment-emergent adverse events 16 weeks Number of Treatment-emergent adverse events including serious adverse events
- Secondary Outcome Measures
Name Time Method Measurement of HBV-DNA decline 40 weeks Measurement of HBV-DNA decline (Δ log10)
Measurement of HBcrAg decline 40 weeks Measurement of HBcrAg decline (Δ log10)
Measurement of HBV-pgRNA decline 40 weeks Measurement of HBV-pgRNA decline (Δ log10)
Concentration of C4 - Pharmacodynamic biomarker 40 weeks Assessment of concentrations of plasma C4 (7α hydroxy 4 cholesten 3 one)
Measurement of HBsAg decline 40 weeks Measurement of HBsAg decline (Δ log10)
Concentration of EYP001a - Pharmacokinetic 20 weeks Assessment of fasted plasma concentrations of EYP001a or any active metabolites using a validated liquid chromatography-mass spectrometry
Concentration of FGF19 - Pharmacodynamic biomarker 40 weeks Assessment of concentrations of plasma FGF19 over time (Fibroblast Growth Factor 19)
Concentration of Bile Acids - Pharmacodynamic biomarker 40 weeks Assessment of concentrations over time of plasma Bile Acids (chenodeoxycholic acid, deoxycholic acid, lithocholic acid)
Trial Locations
- Locations (6)
ENYO PHARMA Investigative site KR01
🇰🇷Busan, Korea, Republic of
ENYO PHARMA Investigative site TW03
🇨🇳Kaohsiung, Taiwan
ENYO PHARMA Investigative site TW04
🇨🇳Kaohsiung, Taiwan
ENYO PHARMA Investigative site TW01
🇨🇳Taipei, Taiwan
ENYO PHARMA Investigative site TW02
🇨🇳Taoyuan, Taiwan
ENYO PHARMA Investigative site HK01
🇭🇰Hong Kong, Hong Kong